The goal of this work is to determine the structural organization of the individual globin genes in chromatin. Pancreatic DNAse I and spleen DNAse II are used as probes of the structure of the globin genses and flanking DNA sequences in nuclear chromatin. Ultimately we wish to obtain a fraction of chromatin enriched in transcribed sequences. Current work focuses on the mouse erythroleukemia (MEL) cell model. Earlier studies had shown that the globin genes in nuclei from induced and uninduced MEL cells were equally sensitive to fairly extensive digestion with DNAse I. Our current efforts are focused on attempting to define more subtle differences in chromatin structure using limited DNAse I digestion. If these techniques are successful, similar analysis of the individual globin genes in nuclei from sheep and human erythroid cells will be performed to define changes in chromatin structural domains during development as the individual genes are selectively expressed. Fusion of mouse erythroleukemia cells to human fibroblasts results in stable hybrid cells which include chromosome 11. Induction of cells leads to production of mouse and human beta mRNA but the human gamma gene is not activated. By probing the chromatin structure in the nuclei of such hybrid cells with DNAse I we have shown that the beta but not the gamma gene is in an active conformation.